Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT

Paolo A Muraro¹, Alice Mariottini^{2

3}, Raffaella Greco⁴, Joachim Burman⁵, Ellen Iacobaeus^{6

7}, Matilde Inglese^{8

9}, John A Snowden^{10

11}, Tobias Alexander^{12

13}, Maria Pia Amato^{2

14}, Lars Bø¹⁵, Giacomo Boffa⁸, Olga Ciccarelli^{16

17}, Jeffrey A Cohen¹⁸, Tobias Derfuss^{19

20}, Dominique Farge^{21

22}, Mark S Freedman^{23

24}, Maria Gaughan²⁵, Christoph Heesen²⁶, Majid Kazmi^{27

28

29}, Kirill Kirzigov³⁰, Per Ljungman^{31

32}, Gianluigi Mancardi⁸, Roland Martin^{33

34

35}, Varun Mehra^{27

29}, Lucia Moiola³⁶, Riccardo Saccardi³, Mar Tintoré^{37

38

39}, Bruno Stankoff^{40

41}, Basil Sharrack^{42

43}; Attendees of the ECTRIMS Focused Workshop on HSCT

Collaborators, Affiliations

Collaborators

Attendees of the ECTRIMS Focused Workshop on HSCT:
Yolanda Blanco, Franziska Di Pauli, Gavin Giovannoni, Cheryl Hemingway, Azza Izmail, Iljias Jelcic, Ludwig Kappos, Luisa Klotz, Anne Kristine Lehmann, Marcin Mycko, Albert Saiz, Joost Smolders, Sandra Vukusic, Barbara Willekens, Helene Zephir

Affiliations

¹ Department of Brain Sciences, Faculty of Medicine, Imperial College, London, UK. p.muraro@imperial.ac.uk.
² Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
³ Careggi University Hospital, Florence, Italy.
⁴ Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
⁵ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁶ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁷ Department of Clinical Neurology, Karolinska University Hospital, Stockholm, Sweden.
⁸ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
⁹ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁰ Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
¹¹ Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
¹² Department of Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹³ German Rheumatology Research Centre, Berlin - A Leibniz Institute, Berlin, Germany.
¹⁴ IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
¹⁵ Department of Neurology, Haukeland University Hospital, and Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹⁶ Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹⁷ National Institute for Health and Care Research, University College London Hospitals Biomedical Research Centre, London, UK.
¹⁸ Mellen Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
¹⁹ Departments of Neurology and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
²⁰ Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University of Basel, Basel, Switzerland.
²¹ Internal Medicine Unit (UF04) CRMR MATHEC, Maladies auto-immunes et thérapie cellulaire; Saint-Louis Hospital, AP-HP, Paris-Cite University, Paris, France.
²² Department of Medicine, McGill University, Montreal, Quebec, Canada.
²³ University of Ottawa, Department of Medicine Ottawa, Ottawa, Ontario, Canada.
²⁴ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
²⁵ Department of Neurology, Beaumont Hospital, Dublin, Ireland.
²⁶ Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁷ Guy's and St Thomas' NHS Trust, King's College Hospital NHS Trust, London, UK.
²⁸ London Bridge Hospital, London, UK.
²⁹ Department of Haematological Medicine, King's College Hospital, London, UK.
³⁰ Nikolay Blokhin National Medical Research Center of Oncology, Moscow, Russia.
³¹ Department. of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Karolinska Comprehensive Cancer Center, Stockholm, Sweden.
³² Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
³³ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
³⁴ Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Stockholm, Sweden.
³⁵ Cellerys AG Schlieren, Schlieren, Switzerland.
³⁶ Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
³⁷ Multiple Sclerosis Centre of Catalonia, Department of Neurology, Barcelona, Spain.
³⁸ Vall d'Hebron University Hospital, Vall d Hebron Research Institute, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
³⁹ Universitat de Vic (UVIC-UCC), Vic, Spain.
⁴⁰ Sorbonne Université, ICM, Paris Brain Institute, CNRS, Inserm, Paris, France.
⁴¹ Neurology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
⁴² Department of Neuroscience, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
⁴³ Sheffield NIHR Translational Neuroscience BRC, University of Sheffield, Sheffield, UK.

PMID: 39814869
DOI: 10.1038/s41582-024-01050-x

Review

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT

Paolo A Muraro et al. Nat Rev Neurol. 2025 Mar.

. 2025 Mar;21(3):140-158.

doi: 10.1038/s41582-024-01050-x. Epub 2025 Jan 15.

Authors

Collaborators

Attendees of the ECTRIMS Focused Workshop on HSCT:
Yolanda Blanco, Franziska Di Pauli, Gavin Giovannoni, Cheryl Hemingway, Azza Izmail, Iljias Jelcic, Ludwig Kappos, Luisa Klotz, Anne Kristine Lehmann, Marcin Mycko, Albert Saiz, Joost Smolders, Sandra Vukusic, Barbara Willekens, Helene Zephir

Affiliations

¹ Department of Brain Sciences, Faculty of Medicine, Imperial College, London, UK. p.muraro@imperial.ac.uk.
² Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
³ Careggi University Hospital, Florence, Italy.
⁴ Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
⁵ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁶ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁷ Department of Clinical Neurology, Karolinska University Hospital, Stockholm, Sweden.
⁸ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
⁹ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁰ Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
¹¹ Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
¹² Department of Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹³ German Rheumatology Research Centre, Berlin - A Leibniz Institute, Berlin, Germany.
¹⁴ IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
¹⁵ Department of Neurology, Haukeland University Hospital, and Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹⁶ Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹⁷ National Institute for Health and Care Research, University College London Hospitals Biomedical Research Centre, London, UK.
¹⁸ Mellen Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
¹⁹ Departments of Neurology and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
²⁰ Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University of Basel, Basel, Switzerland.
²¹ Internal Medicine Unit (UF04) CRMR MATHEC, Maladies auto-immunes et thérapie cellulaire; Saint-Louis Hospital, AP-HP, Paris-Cite University, Paris, France.
²² Department of Medicine, McGill University, Montreal, Quebec, Canada.
²³ University of Ottawa, Department of Medicine Ottawa, Ottawa, Ontario, Canada.
²⁴ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
²⁵ Department of Neurology, Beaumont Hospital, Dublin, Ireland.
²⁶ Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁷ Guy's and St Thomas' NHS Trust, King's College Hospital NHS Trust, London, UK.
²⁸ London Bridge Hospital, London, UK.
²⁹ Department of Haematological Medicine, King's College Hospital, London, UK.
³⁰ Nikolay Blokhin National Medical Research Center of Oncology, Moscow, Russia.
³¹ Department. of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Karolinska Comprehensive Cancer Center, Stockholm, Sweden.
³² Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
³³ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
³⁴ Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Stockholm, Sweden.
³⁵ Cellerys AG Schlieren, Schlieren, Switzerland.
³⁶ Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
³⁷ Multiple Sclerosis Centre of Catalonia, Department of Neurology, Barcelona, Spain.
³⁸ Vall d'Hebron University Hospital, Vall d Hebron Research Institute, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
³⁹ Universitat de Vic (UVIC-UCC), Vic, Spain.
⁴⁰ Sorbonne Université, ICM, Paris Brain Institute, CNRS, Inserm, Paris, France.
⁴¹ Neurology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
⁴² Department of Neuroscience, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
⁴³ Sheffield NIHR Translational Neuroscience BRC, University of Sheffield, Sheffield, UK.

PMID: 39814869
DOI: 10.1038/s41582-024-01050-x

Abstract

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD). Furthermore, treatment and monitoring protocols, rehabilitation and other supportive care before and after AHSCT need to be optimized. To address these issues, we convened a European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop in partnership with the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party, in which evidence and key questions were presented and discussed by experts in these diseases and in AHSCT. Based on the workshop output and subsequent written interactions, this Consensus Statement provides practical guidance and recommendations on the use of AHSCT in MS and NMOSD. Recommendations are based on the available evidence, or on consensus when evidence was insufficient. We summarize the key evidence, report the final recommendations, and identify areas for further research.

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Conflict of interest statement

Competing interests: P.A.M. has received fees from consulting for Cellerys, Jasper Therapeutics and Magenta Therapeutics, all outside the submitted work. A.M. has received speaking honoraria from Biogen, Janssen, Novartis, Sanofi and Viatris, all outside the submitted work. R.G. has received speaker honoraria from Biotest, Magenta, Medac and Pfizer, all outside the submitted work. E.I. has received speaker fees and honoraria for advisory boards from Biogen, Merck and Sanofi-Genzyme, and an unrestricted research grant from Sanofi-Genzyme. M.I. is co-Editor of Multiple Sclerosis Journal and she has received honoraria for participating in educational activities or advisory boards for Biogen, Janssen, Merck, Novartis, Roche and Sanofi. T.A. has received honoraria and/or travel grants from Amgen, AstraZeneca, GSK and Neovii, and study support from Amgen, Janssen-Cilag and Miltenyi. M.P.A. has served on scientific advisory boards for Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva; has received speaker honoraria from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva; has received research grants for her Institution from Biogen, Merck, Novartis, Roche and Sanofi-Genzyme. She is co-Editor of Multiple Sclerosis Journal and Associate Editor of Frontiers in Neurology. G.B. was supported by a research fellowship FISM – Fondazione Italiana Sclerosi Multipla 019/BR/016, and financed or co-financed with the ‘5 per mille’ public funding. O.C. has received personal compensation for consulting for Biogen, Merck and Novartis, and she serves as deputy Editor of Neurology. J.A.C. has received personal compensation for consulting for Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INMune, and Sandoz, and serves as an Editor of Multiple Sclerosis Journal. T.D. has received speaker fees, research support, travel support, and/or served on advisory boards or steering committees of Alexion, Biogen, Celgene, GeNeuro, MedDay, Merck, Novartis, Roche and Sanofi-Genzyme; he has received research support from Swiss National Research Foundation, University of Basel, and the Swiss MS Society. M.G. has received educational support from Novartis and has an advisory board role for Merck. C.H. has received funding support, speaker honoraria and travel grants from Merck, Novartis and Roche. R.M. has received unrestricted grants from Biogen, Novartis, Roche and Third Rock; has advisory roles and has given lectures for Biogen, CellProtect, Genzyme, Neuway, Novartis, Roche, Swiss Rockets and Third Rock; is a patent holder and co-holder on patents for daclizumab in MS, JCV VP1 for vaccination against PML, JCV-specific neutralizing antibodies to treat PML, and antigen-specific tolerization with peptide-coupled cells and novel autoantigens in MS; is a co-founder of Abata, Cambridge, MA, USA (adoptive Treg therapy); and is a co-founder and employee of Cellerys. L.M. has received compensation for speaking activities and/or consulting services from Alexion, Biogen, Celgene, Merck, Novartis, Roche and Sanofi. M.T. has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Immunic Therapeutics, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Teva and Viela Bio; is on data safety monitoring boards for Parexel and UCB Biopharma; and is on the Relapse Adjudication Committee for Imcyse. B. Stankoff has received research support (to the institution) from Merck, Novartis and Roche, and personal speaker fees from Biogen, Janssen, Merck, Novartis and Sanofi. The other authors declare no competing interests.

References

1. Muraro, P. A. Resetting tolerance in autoimmune disease. Science 380, 470–471 (2023). - PubMed - DOI
1. Snowden, J. A. et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022. Bone Marrow Transpl. 57, 1217–1239 (2022). - DOI
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1. Muraro, P. A. et al. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat. Rev. Neurol. 13, 391–405 (2017). - PubMed - DOI

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Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT

Collaborators

Affiliations

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

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Medical